Mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria

Alternate names

Mitochondrial encephalomyopathy aminoacidopathy; Mitochondrial dna depletion syndrome, encephalomyopathic form with methylmalonic aciduria, autosomal recessive; Booth-Haworth-Dilling syndrome; mtDNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria; SUCLA2-Related Mitochondrial DNA Depletion Syndrome, Encephalomyopathic Form with Methylmalonic Aciduria; Mitochondrial DNA depletion syndrome 9

Definition

Mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria (MTDPS9) affects the brain, nervous system, and muscles.

Epidemiology

It is unclear how many people have mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria. There have been about 30 cases of this condition described in the medical literature.

Cause

• Mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria occurs when the SUCLG1 gene is not working correctly.
• DNA changes known as pathogenic variants are responsible for making genes work incorrectly or sometimes, not at all.

Inheritance

Autosomal recessive inheritance, a 25% chance

Mitochodrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria is inherited in an autosomal recessive pattern.

• All individuals inherit two copies of each gene. Autosomal means the gene is found on one of the numbered chromosomes found in both sexes. Recessive means that both copies of the responsible gene must be have a pathogenic variant to have the condition.
• People with autosomal recessive conditions inherit one variant from each of their parents. The parents, who each have one gene variant, are known as carriers.
• Carriers of an autosomal recessive condition typically do not have any signs or symptoms (they are unaffected). When two carriers of an autosomal recessive condition have children, there is a 25% (1 in 4) chance to have a child with the condition.

Onset

Symptoms typically begin in early infancy and get worse over time, leading to early death.

Signs and symptoms

• The following list includes the most common signs and symptoms in people with mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria.
• These features may be different from person to person.
• Some people may have more symptoms than others and they can range from mild to severe. This list does not include every symptom that has been described in the condition.

Symptoms of mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria may include:

• Muscle weakness
• Difficulty feeding
• Inability to sit or hold the head up
• Hearing loss
• Poor growth (failure to thrive)
• Difficulty breathing due to muscle weakness
• Developmental delay
• Cognitive impairment

Other symptoms include high levels of lactic acid in the blood and low blood sugar.

Diagnosis

• Mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria is diagnosed based on the symptoms, clinical exam, imaging studies, and the removal of a piece of muscle for examination (muscle biopsy).
• In addition, blood and urine testing to look for high levels of lactic acid and methylmalonic acid may be helpful.
• The diagnosis may be confirmed by the results of genetic testing.

Treatment

• Physical therapy to maintain muscle function and prevent joint contractures.
• Antiepileptic drugs for seizures
• Nasogastric or gastrostomy tube as needed to assure adequate caloric intake
• chest physiotherapy, aggressive antibiotic treatment of chest infections, and respiratory aids such as assisted nasal ventilation or use of a tracheostomy and ventilator when indicated
• Bracing to treat scoliosis or kyphosis
• Blepharoplasty for significant ptosis
• Hearing aids/cochlear implantation for sensorineural hearing loss.

NIH genetic and rare disease info

• NIH info on Mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria

Mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria is a rare disease.